The overall objectives of the proposed research are to study the functioning of presynaptic receptor mechanisms regulating norepinephrine release in normotensive and experimental hypertensive animals. In addition, the influence of treatment with clonidine and propranolol on these presynaptic control mechanisms will also be determined. In anesthetized dogs, presynaptic alpha-receptor, beta-receptor, angiotensin II and prostaglandin mediated control mechanisms will be studied by evaluating the effects of appropriate agonists on nerve stimulation-induced release of the neurotransmitter from the heart and the kidney. Under in vitro conditions, the operation of these presynaptic receptor mechanisms in the renal and mesenteric vasculature of rats and the mesenteric vasculature of dogs will be investigated by measuring the release of 3H-transmitter during periarterial nerve stimulation following the loading of these tissues with 3H-norepinephrine. Appropriate receptor agonists and antagonists will be used to identify these receptor mechanisms and their possible dysfunctioning in the experimental hypertensive animals. These experiments should be helpful in determining the possible factors responsible for causing an overactivity of sympathetic nervous system which is reported to be associated with development and maintenance of hypertension.